Mechanisms responsible for the initiation and progression of CLL

Dr Alison Michie

Research interests

The Molecular Lymphopoiesis group was established in 2005 and focuses on the molecular events that induce haemopoietic stem cells (HSCs) to commit and differentiate towards the B and T lymphocyte lineages. During the course of our studies defining the role of specific signalling molecules that control the early stages of both B and T cell development, we established that PKC plays an essential role in mediating differentiation and proliferation signals downstream of the pre-TCR complex in vivo. An extension of these studies to investigate the role of PKC during B cell development revealed that inhibition of PKC signalling acts as an oncogenic trigger for developing B lymphocytes, resulting in the spontaneous generation of a population of cells that phenotypically resemble human B cell chronic lymphocytic leukaemia (CLL). Therefore our future studies aim to define the mechanisms that control normal lymphoid and leukaemic cell development using the experimental systems we have established.

Research Interests

We aim to identify molecular events that initiate the development and maintenance of CLL, which in turn will assist in the identification of novel therapeutic targets. Validating of the importance of these novel targets in the development of CLL, in addition to testing of novel targeted compounds, will be carried out in patient-derived CLL samples. We have established an extensive cell bank, representative of the prognostic CLL patient subgroups to facilitate these studies. Moreover, we have developed in vitro culture conditions that mimic the pro-survival and pro-proliferative microenvironments found within lymphoid organs of patients where CLL cells persist. These systems will provide critical information regarding the likely efficacy of novel therapeutic agents to induce CLL cell death in vivo.